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HEALTBSCIENCESSTANMBD 


HX00035114 


Miylogenetic  Association 
_.i  Relation  to  Certain 
Medical     Problems 


Ether  Day  Address 
1910 


I  hRX^V 


■ 


(Columbia  Httmrrsttg 
in  tl}t  (Cup,  nf  Nm  ^nrk 

(CnllprjiP  nf  ffhtjairiana  arto  ^arginma 


i&tUxmtt   IGtbrarg 


Phylogenetic  Association 
in  Relation  to  Certain 
Medical    Problems 


GEORGE  W.  CRILE,  M.D. 

Cleveland,  Ohio 


Ether  Day  Address 
1910 


Digitized  by  the  Internet  Archive 

in  2010  with  funding  from 

Open  Knowledge  Commons 


http://www.archive.org/details/phylogeneticassoOOcril 


PHYLOGENETIC     ASSOCIATION     IN    RELA- 
TION TO  CERTAIN  MEDICAL 
PROBLEMS.* 

The  discovery  of  the  anesthetic  properties  of  ether 
and  its  practical  application  to  surgery  must  always 
stand  as  one  of  the  great  achievements  of  medicine. 
It  is  eminently  fitting  that  the  anniversary  of  that 
notable  day,  when  the  possibilities  of  ether  were  first 
made  known  to  the  world,  should  be  celebrated  within 
these  walls,  and  whatever  the  topic  of  your  Ether 
Day  orator,  he  must  fittingly  first  pause  to  pay  tribute 
to  that  great  event  and  to  the  master  surgeons  of  the 
Massachusetts  General  Hospital.  On  this  occasion, 
on  behalf  of  the  dumb  animals  as  well  as  on  behalf  of 
suffering  humanity,  I  express  a  deep  sense  of  grati- 
tude for  the  blessings  of  anesthesia.  Two  years  ago 
an  historical  appreciation  of  the  discovery  of  ether 
was  here  presented  by  Professor  Welch,  and  last 
year  an  address  on  medical  research  was  given  by 
President  Eliot.  I,  therefore,  will  not  attempt  a  gen- 
eral address,  but  will  present  an  experimental  and 
clinical  research. 

Time  will  permit  the  presentation  of  only  the  sum- 
maries of  the  large  amount  of  data.  The  great 
assistance  rendered  by  my  associates,  Dr.  D.  H. 
Dolley,  Dr.  H.  G.  Sloan,  Dr.  J.  B.  Austin  and 
Dr.  M.  L.  Mentenf,  I  acknowledge  with  gratitude. 


♦Address  delivered  at  the  Massachusetts  General  Hospital  on  the 
sixty-fourth  anniversary  of  Ether  Day,  Oct.  15,  1910. 

+From  H.  K.  Cushing  Laboratory  of  Experimental  Medicine,  Western 
Reserve  University,  Cleveland. 

3 


The  scope  of  the  title  of  this  paper  may  be  ex- 
plained by  a  concrete  example. 

When  a  barefoot  boy  steps  on  a  sharp  stone  there  is 
an  immediate  discharge  of  nervous  energy  in  his  effort 
at  escape  from  the  wounding  stone.  This  is  not  a  vol- 
untary act.  It  is  not  due  to  his  own  personal  experience 
(i.e.,  his  ontogeny),  but  is  due  to  the  experience  of 
his  progenitors  during  the  vast  periods  of  time  re- 
quired for  the  evolution  of  the  species  to  which  he 
belongs,  i.e.,  his  phylogeny.  The  wounding  stone 
made  an  impression  upon  the  nerve  receptors  in  the 
foot  similar  to  the  innumerable  injuries  which  gave 
origin  to  this  nerve  mechanism  itself  during  the  boy's 
vast  phylogenetic  or  ancestral  experience.  The  stone 
supplied  the  phylogenetic  association,  and  the  appro- 
priate discharge  of  nervous  energy  automatically 
followed.  If  the  sole  of  the  foot  is  repeatedly  bruised 
or  crushed  by  the  stone,  shock  may  be  produced.  If 
the  stone  be  only  lightly  applied,  then  there  is  also  a 
discharge  of  nervous  energy  from  the  sensation  of 
tickling.  The  body  has  had  implanted  within  it  in  a 
similar  manner  other  mechanisms  of  ancestral  or  phy- 
logenetic origin  whose  purpose  is  the  discharge  of 
nervous  energy  for  the  good  of  the  individual.  In 
this  paper  I  shall  discuss  the  origin  and  mode  of  action 
of  some  of  these  mechanisms  including  certain  phases 
of  anesthesia. 

The  word  anesthesia  —  meaning  without  feeling  — 
describes  accurately  the  effect  of  ether  in  anesthetic 
dosage.  Although  no  pain  is  felt  in  operations  under 
inhalation  anesthesia,  the  nerve  impulses  set  up  by  a 
surgical  operation  still  reach  the  brain.  We  know 
that  not  every  portion  of  the  brain  is  fully  anesthe- 
tized,   since  surgical  anesthesia  does  not  kill.     The 

4 


question  then  is,  What  effect  has  trauma  under  surgi- 
cal anesthesia  upon  the  part  of  the  brain  that  remains 
awake  ?  If,  in  surgical  anesthesia,  the  traumatic 
impulses  cause  an  excitation  of  those  wide-awake 
cells,  are  the  remainder  of  the  cells  of  the  brain, 
despite  anesthesia,  influenced  in  any  way?  If  influ- 
enced, they  are  prevented  by  the  anesthesia  from 
expressing  the  same  in  conscious  perception  or  in 
muscular  action.  Whether  the  anesthetized  cells  are 
influenced  or  not  must  be  determined  by  noting  the 
physiologic  function  after  anesthesia  has  worn  off,  and 
in  animals  by  an  examination  of  the  brain  cells  as 
well.  It  has  long  been  known  that  the  vasomotor,  the 
cardiac  and  the  respiratory  centers  discharge  energy 
in  response  to  traumatic  stimuli  applied  to  various 
sensitive  regions  of  the  body  during  surgical  anesthe- 
sia. If  the  trauma  is  sufficient,  exhaustion  of  the 
entire  brain  is  observed  after  the  effect  of  the  anes- 
thetic is  worn  off ;  that  is  to  say,  despite  the  complete 
paralysis  of  voluntary  motion  and  the  loss  of  conscious- 
ness due  to  ether,  the  traumatic  impulses  that  are 
known  to  reach  the  awake  centers  in  the  medulla  also 
reach  and  influence  every  other  part  of  the  brain.  As 
to  whether  or  not  the  consequent  functional  depression 
and  the  morphologic  alterations  seen  in  the  brain  cells 
may  be  due  to  the  low  blood  pressure  which  follows 
excessive  trauma  is  answered  by  the  following  experi- 
ments, viz  :  the  circulation  of  animals  was  first  ren- 
dered static  by  over-transfusion,  and  was  controlled  by 
a  continuous  blood-pressure  record  on  a  drum,  the 
factor  of  anemia  was  thereby  wholly  excluded  during 
the  application  of  the  trauma  and  during  the  removal 
of  a  specimen  of  brain  tissue  for  histologic  study.  In 
every  such  instance  morphologic  changes  in  the  cells 

5 


of  all  parts  of  the  brain  were  found,  but  it  required 
more  trauma  to  produce  equal  morphologic  changes 
in  animals  protected  against  low  blood  pressure  than 
in  animals  whose  blood  pressure  gradually  declined  in 
the  course  of  the  experiments. 

In  the  cortex  and  in  the  cerebellum,  the  changes  in 
the  brain  cells  were  in  every  instance  more  marked 
than  in  the  medulla.  There  is  also  strong  negative 
evidence  that  traumatic  impulses  are  not  excluded  by 
ether  anesthesia  from  the  part  of  the  brain  that  is 
apparently  asleep.      This  evidence  is  as  follows  : 

If  the  factor  of  fear  be  excluded,  and  if  in  addition 
the  traumatic  impulses  are  prevented  from  reaching 
the  brain  by  cocaine  blocking,  then,  despite  the  inten- 
sity or  the  duration  of  the  trauma  within  the  zone  so 
blocked,  there  follows  no  exhaustion  after  the  effect 
of  the  anesthetic  disappears,  and  no  morphologic 
changes  are  noted  in  the  brain  cells.  A  still  further 
negative  evidence  that  inhalation  anesthesia  offers 
little  or  no  protection  to  the  brain  cells  from  trauma  is 
derived  from  the  following  experiment  :  A  dog  whose 
spinal  cord  had  been  divided  at  the  level  of  the  first 
dorsal  segment,  and  then  kept  in  good  condition  for 
two  months,  showed  a  recovery  of  the  spinal  reflexes, 
such  as  the  scratch  reflex,  etc.  This  animal  is  known 
as  a  "spinal'1  dog.  Now,  in  this  animal  the  abdo- 
men and  hind  extremities  have  no  direct  nerve  con- 
nection with  the  brain.  In  such  a  dog  a  continuous 
severe  trauma  of  the  abdominal  viscera  and  of  the 
hind  extremities  lasting  four  hours  was  accompanied 
by  but  slight  change  in  either  the  circulation  or  in  the 
respiration,  and  no  microscopical  alteration  of  the 
brain  cells.  Judging  from  a  large  number  of  experi- 
ments on  normal  dogs  under  ether,  such   an  amount 

6 


of  trauma  would  have  caused  not  only  a  complete 
physiologic  exhaustion  of  the  brain,  but  also  morpho- 
logic alterations  of  all  of  the  brain  cells  and  physical 
destruction  of  many.  We  must,  therefore,  conclude 
that,  although  ether  anesthesia  produces  unconscious- 
ness, it  apparently  protects  none  of  the  brain  cells  against 
exhaustion  from  the  trauma  of  surgical  operations  ; 
ether  is,  so  to  speak,  but  a  veneer.  Under  nitrous 
oxide  anesthesia  there  is  approximately  only  one- 
fourth  the  exhaustion  on  equal  trauma  as  under  ether  ; 
either  nitrous  oxide  protects  or  ether  predisposes  to 
exhaustion  under  trauma.  With  this  as  a  point  of 
departure  we  will  inquire  into  the  cause  of  this  ex- 
haustion of  the  brain  cells. 

On  the   Cause  of  the  Exhaustion  of  the  Brain   Cells 

from  Trauma  of  Various  Parts  of  the  Body  Under 

Inhalation  Anesthesia. 

Numerous  experiments  on  animals  upon  the  effect 
of  ether  anesthesia  per  se,  i.e.,  ether  anesthesia  with- 
out trauma,  showed  that  although  certain  changes 
were  seen  there  was  neither  the  characteristic  physio- 
logic exhaustion  after  the  anesthesia  had  worn  off  nor 
were  there  seen  the  characteristic  changes  in  the 
brain  cells.  Turning  to  trauma,  in  a  study  of  the 
behavior  of  individuals  as  a  whole  under  deep  and 
under  light  anesthesia,  we  at  once  found  the  cue  to 
the  discharge  of  energy,  —  the  consequent  physiologic 
exhaustion  and  the  morphologic  changes  in  the  brain 
cells. 

If,  in  the  course  of  abdominal  operations,  rough 
manipulation  of  the  parietal  peritoneum  is  made,  there 
is  frequently  observed  a  marked  increase  in  the  res- 
piratory rate  and  an  increase  in  the  expiratory  force, 

7 


even  to  the  extent  of  an  audible  expiratory  groan. 
Under  light  ether  anesthesia  severe  manipulation  of 
the  peritoneum  often  causes  such  vigorous  contrac- 
tions of  the  abdominal  muscles  that  the  operator  may 
be  greatly  hindered  in  his  work. 

Among  the  unconscious  responses  to  trauma  under 
ether  anesthesia  are  purposeless  moving,  withdrawing 
of  the  injured  part,  and  if  the  anesthesia  is  sufficiently 
light  and  the  trauma  sufficiently  strong,  there  may  be 
an  effort  directed  toward  escape  from  the  injury.  In 
injury  under  ether  anesthesia  every  grade  of  response 
may  be  seen,  from  the  slightest  change  in  the  respira- 
tion or  in  the  blood  pressure  to  a  vigorous  defensive 
struggle.  As  to  the  purpose  of  these  subconscious 
movements  in  response  to  injury,  there  can  be  no 
doubt,  —  they  are  efforts  at  escape  from  the  injury. 

Can  anyone  picture  the  actual  result  of  a  formi- 
dable abdominal  operation  extending  over  a  period  of 
half  an  hour  or  more  in  an  unanesthetized  human 
patient  if  extensive  adhesions  are  broken  up,  or  if  a 
large  tumor  is  dislodged  from  its  bed  ?  In  such  a  case 
would  not  the  nervous  system  discharge  its  energy  to 
the  utmost  in  efforts  to  escape  from  the  injury,  and 
would  the  patient  not  suffer  complete  exhaustion  ?  If 
the  traumata,  under  inhalation  anesthesia,  be  suffi- 
ciently strong  and  repeated  in  sufficient  numbers,  the 
brain  cells  will  finally  be  deprived  of  their  discharge- 
able nervous  energy  and  become  exhausted  just  as 
exhaustion  follows  a  strenuous  and  too  prolonged 
muscular  exertion,  for  example,  such  as  is  seen  in 
endurance  tests.  Whether  the  nerve  energy  of  the 
brain  is  discharged  by  injury  under  anesthesia,  or 
whether  by  ordinary  muscular  exertion,  identical  mor- 
phologic changes    are    seen   in    the    nerve  cells.     In 

8 


shock  from  injury,  in  exhaustion  from  overwork 
(Hodge  and  Dolley)  and  in  exhaustion  from  pure 
fear,  the  general  functional  weakness  is  similar,  —  in 
each  a  certain  length  of  time  is  required  to  effect  re- 
covery, and  in  each  there  are  morphologic  changes  in 
the  brain  cells.  It  is  quite  clear  that  in  each  of  these 
cases  the  altered  function  and  form  of  the  brain  cells 
are  due  to  an  excessive  discharge  of  nervous  energy. 
This  brings  us  to  the  next  question,  viz  :  what  de- 
termines the  discharge  of  energy  from  trauma  with  or 
without  inhalation  anesthesia  ? 

On  the   Cause  of  the  Discharge  of  Nervous  Energy 

from  Trauma  in  Animals  Under  Inhalation 

Anesthesia  as  Well  as  in  the  Normal 

State  with  Special  Reference  to 

Medical  Problems. 

I  looked  into  this  problem  from  many  view-points 
and  there  seemed  to  be  no  solution  until  it  occurred  to 
me  to  seek  the  explanation  in  certain  of  the  postulates 
which  make  up  the  doctrine  of  evolution.  I  realize 
fully  the  difficulty  and  the  danger  in  attempting  to 
reach  the  generalization  which  I  shall  make  later  and 
in  the  hypothesis  I  shall  propose.  There  is,  of 
course,  no  direct  final  proof  of  the  truth  of  even  the 
doctrine  of  evolution.  It  is  idle  to  consider  any  ex- 
perimental research  into  the  cause  of  phenomena  that 
have  by  natural  selection  required  millions  of  years  to 
develop.  Nature  has  made  the  experiments  on  a 
world-wide  scale  ;  the  data  are  before  us  for  interpre- 
tation. Darwin  could  do  no  more  than  collect  all 
available  facts  and  then  frame  an  hypothesis  that  best 
harmonized  the  facts.  Sherrington,  that  masterly 
physiologist,  in  his  volume  entitled  "  The  Integrative 

9 


Action  of  the  Nervous  System,"  shows  clearly  how 
the  central  nervous  system  was  built  up  in  the  proc- 
ess of  evolution.  Sherrington  has  made  free  use  of 
Darwin's  doctrine  in  explaining  physiologic  functions, 
just  as  anatomists  have  extensively  utilized  it  in  the 
explanation  of  the  genesis  of  anatomical  forms.  I 
will  assume,  therefore,  that  the  discharge  of  nervous 
energy  is  accomplished  by  the  application  of  the  law 
of  inheritance  and  association,  and  that  this  hypothesis 
will  explain  many  clinical  phenomena.  I  shall  present 
such  evidence  in  favor  of  this  hypothesis  as  time  and 
my  limitations  will  admit,  after  which  I  shall  point  out 
certain  clinical  facts  that  may  be  explained  on  this 
hypothesis. 

According  to  the  doctrine  of  evolution,  every  func- 
tion owes  its  origin  to  natural  selection  in  the  struggle 
for  existence.  In  the  lower  and  simpler  animal  life, 
indeed,  in  our  human  progenitors  as  well,  existence 
depended  principally  upon  the  success  with  which 
three  great  purposes  were  achieved,  viz  :  (l)  self- 
defense  against  or  escape  from  enemies  ;  (2)  the 
acquisition  of  food  ;  and  (3)  procreation  ;  and  these 
were  virtually  the  only  purposes  for  which  nervous 
energy  was  discharged.  In  its  last  analysis  in  a  bio- 
logic sense  this  statement  holds  for  man  of  to-day. 
Disregarding  for  the  present  the  expenditure  of  energy 
for  procuring  food  and  for  procreation,  we  will  consider 
the  discharge  of  energy  in  self-preservation.  The 
mechanisms  for  self-defense  which  we  now  possess 
were  developed  in  the  course  of  vast  periods  of  time 
from  the  lowest  forms  through  all  the  intermediary 
stages  to  our  present  estate.  One  would  expect, 
therefore,  that  we  are  now  in  possession  of  mechan- 
isms which  still  may  discharge  energy  on  adequate 


stimulation  but  are  not  suited  to  our  present  needs. 
We  shall  point  out  such  examples.  As  Sherrington 
has  stated,  there  is  interposed  between  ourselves  and 
the  environment  in  which  we  are  immersed,  our  skin, 
in  which  are  implanted  many  receptors  for  receiving 
specific  stimuli  which  are  transmitted  to  the  brain. 
When  these  stimuli  reach  the  brain,  there  is  a  specific 
response  principally  in  the  form  of  muscular  action. 
Now,  each  receptor  can  only  be  adequately  stimulated 
by  the  particular  factor  or  factors  in  the  environment 
which  created  the  necessity  for  the  receptor  in  ques- 
tion. Thus  there  have  arisen  receptors  for  touch,  for 
temperature,  for  pain,  etc.  The  receptors  for  pain 
have  been  designated  noci-ceptors  (nocuous  or  harmful 
influences)  by  Sherrington. 

On  the  basis  of  natural  selection,  only  the  regions 
of  the  body  that  have  been  during  long  periods  of  time 
exposed  to  injury  could  have  developed  noci-ceptors. 
On  this  ground  the  finger,  because  it  is  exposed,  should 
have  many  noci-ceptors,  while  the  brain,  though  the 
most  important  organ  of  the  body,  because  it  has  been 
during  a  vast  period  of  time  protected  by  a  skull,  should 
have  no  noci-ceptors.  Realizing  that  this  point  is  a 
crucial  one,  Dr.  Sloan  and  I  made  a  series  of  careful 
experiments.  The  cerebral  hemispheres  of  dogs  were 
exposed  by  removal  of  the  skull  and  dura  under  ether 
anesthesia  and  under  local  anesthesia.  Then  various 
portions  of  the  hemispheres  were  slowly  but  completely 
destroyed  by  rubbing  with  a  piece  of  gauze.  In  some 
instances  the  hemisphere  was  destroyed  by  burning. 
In  no  instance  was  there  more  than  a  slight  response 
of  the  centers  governing  circulation  and  respiration, 
and  there  was  no  morphologic  change  noted  in  a  histo- 
logic study  of  the  brain  cells  of  the  uninjured  hemis- 


phere.  The  experiment  was  as  completely  negative 
as  the  experiments  on  the  "spinal"  dog.  Clinically 
I  have  confirmed  the  experimental  findings  in  the 
course  of  explorations  for  brain  tumor  with  a  probe  in 
conscious  patients.  Such  explorations  elicited  neither 
pain  nor  evidence  of  altered  physiologic  functions. 
The  brain,  therefore,  contains  no  mechanism,  —  no 
noci-ceptors, — the  direct  stimulation  of  which  could 
cause  a  discharge  of  nervous  energy  in  a  self-defensive 
action.  That  is  to  say,  direct  injury  of  the  brain  can 
cause  no  purposeful  nerve  muscular  action,  while  direct 
injury  of  the  finger  does  cause  purposive  nerve  mus- 
cular action.  In  like  manner,  the  deeper  portions  of 
the  spinal  region  have  been  sheltered  from  trauma, 
and  they  too  show  but  little  power  of  causing  a  dis- 
charge of  nervous  energy  on  receiving  trauma.  The 
various  tissues  and  organs  of  the  body  are  differently 
endowed  with  injury  receptors,  or  the  noci-ceptors  of 
Sherrington.  The  abdomen  and  chest  when  trauma- 
tized stand  first  in  their  facility  for  causing  the  dis- 
charge of  nervous  energy,  i.e.,  they  stand  first  in  shock- 
production.  Then  follow  the  extremities,  the  neck  and 
the  back.  It  is  an  interesting  fact  that  this  physical 
type  or  that  physical  type  of  trauma  elicits  different 
responses  as  to  the  discharge  of  energy.  Because  it  is 
such  a  commonplace,  one  scarcelv  realizes  the  impor- 
tance of  the  fact  that  clean-cut  wounds  with  a  razor- 
like knife  cause  the  least  reaction,  while  a  tearing, 
crushing  trauma  causes  the  greatest  response.  It  is 
a  suggestive  fact  that  the  technic  of  the  carnivora  in 
fighting  each  other  and  in  killing  their  prey  is  probably 
the  most  efficient  shock-producing  trauma  known.  In 
the  course  of  evolution  this  may  well  liave  been  the  pre- 
dominating type  of  trauma  to  which  our  progenitors  were 
subjected. 

12 


The  discharge  of  energy  caused  by  an  adequate  me- 
chanical stimulation  of  the  noci-ceptors  is  best  ex- 
plained in  accordance  with  the  law  of  phylogeny  and 
association.  That  is,  injuries  awaken  such  reflex 
actions  as  have  by  natural  selection  been  developed 
for  the  purpose  of  self-protection.  Adequate  stimu- 
lation of  the  noci-ceptors  for  pain  is  not  the  only  means 
of  causing  a  discharge  of  nervous  energy.  Nervous 
energy  may  also  be  discharged  by  adequate  stimula- 
tion of  the  various  ticklish  regions  of  the  body.  The 
entire  skin  surface  of  the  body  contains  delicate  tick- 
lish receptors.  These  receptors  are  closely  related 
to  the  noci-ceptors  for  pain,  and  their  adequate  stimu- 
lation by  an  insect-like  touch  causes  a  discharge  of 
energy  —  a  nerve  muscular  reaction  —  resembling 
that  of  brushing  off  insects.  This  reflex  is  similar  to 
the  scratch  reflex  elicited  in  the  dog.  This  discharge 
of  energy  is  almost  wholly  independent  of  the  will 
and  is  a  self-protective  action  in  the  same  sense  as  is 
the  response  to  pain  stimuli.  The  ear  in  man  and  in 
animals  is  acutely  ticklish, — the  adequate  stimulus 
being  any  foreign  body,  —  especially  a  buzzing  insect- 
like contact.  The  discharge  of  nervous  energy  in 
horses  and  in  cattle  on  adequate  stimulation  of  the 
ticklish  receptors  of  the  ear  is  so  extraordinary  that  in 
the  course  of  evolution  it  must  have  been  of  great  im- 
portance to  the  safety  of  the  animal.  A  similar  tick- 
lish zone  guards  the  nasal  chambers.  The  discharge 
of  energy  here  takes  such  form  as  effectively  to  dis- 
lodge the  foreign  body.  The  larynx  is  exquisitely 
ticklish,  and  in  response  to  adequate  stimulus,  energy 
is  discharged  in  the  production  of  a  vigorous  cough. 
The  mouth  and  pharynx  have  active  receptors  which 
cause  the  rejection  of  nocuous  substances.     The  con- 

13 


junctival  reflex,  though  not  classed  as  ticklish,  is  a 
most  efficient  self-protective  reflex.  I  assume  that 
there  is  no  doubt  as  to  the  meaning  of  the  adequate 
stimuli  and  the  nerve-muscular  response  of  the 
various  ticklish  receptors  of  the  surface  of  the  skin, 
of  the  ear,  the  nose,  and  the  eye,  and  the  larynx. 
These  mechanisms  were  developed  by  natural  selec- 
tion as  protective  measures  against  the  intrusion  of 
insects  and  foreign  bodies  into  regions  of  great  im- 
portance. The  discharge  of  energy  in  these  instances 
is  in  accordance  with  the  law  of  inheritance  and  asso- 
ciation. The  other  ticklish  points  which  are  capable 
of  discharging  vast  amounts  of  energy  are  the  lateral 
chest  wall,  the  abdomen,  the  loins,  the  neck  and  the 
soles  of  the  feet.  The  type  of  adequate  stimuli  of  the 
soles  of  the  feet,  the  distribution  of  the  ticklish  points 
upon  them,  and  the  associated  response  leave  no 
doubt  that  these  ticklish  points  were  long  ago  estab- 
lished as  a  means  of  protection  from  injury.  Under 
present  conditions  they  are  of  little  value  to  man. 

The  adequate  stimulus  for  the  ticklish  points  of  the 
ribs,  the  loins,  the  abdomen  and  the  neck  is  deep 
isolated  pressure,  probably  the  most  adequate  being 
that  of  a  tooth-shaped  body.  The  response  to  tick- 
ling in  these  regions  is  actively  and  obviously  self- 
defensive.  The  horse  discharges  energy  in  the  form 
of  a  kick  ;  the  dog  wriggles  and  makes  a  counter- 
bite  ;  the  man  makes  efforts  at  defense  and  escape. 

There  is  strong  evidence  that  the  deep  ticklish  points 
of  the  body  were  acquired  through  vast  periods  of  fight- 
ing, with  teeth  and  claws.  Even  puppies  at  play  bite 
each  other  in  their  ticklish  points  and  thus  give  a  reca- 
pitulation of  their  ancestral  battles  and  of  the  real  battles 
to  come.     The  mere  fact  that  animals  fight  effectively 

14 


in  the  dark  and  always  according  to  the  habit  of  their 
species  supports  the  belief  that  the  fighting  of  animals  is 
not  an  intellectual  but  a  reflex  process.  There  is  no 
book  of  rules  governing  the  conduct  of  a  fight  between 
animals.  The  sequences  of  events  follow  each  other 
with  such  kaleidoscopic  rapidity  that  the  process  is 
but  a  series  of  automatic  stimulations  and  physiologic 
reactions.  Whatever  the  significance,  it  is  certain 
that  man  did  not  come  either  accidentally  or  without 
purpose  into  possession  of  the  deep  ticklish  regions  of 
his  chest  and  abdomen.  Should  any  one  doubt  the 
vast  power  that  adequate  stimulation  of  these  regions 
possess  in  causing  the  discharge  of  energy,  let  him 
be  bound  hand  and  foot  and  vigorously  tickled  for  an 
hour.  What  would  happen?  He  would  be  as  com- 
pletely exhausted  as  though  he  had  experienced  a 
major  surgical  operation  or  as  if  he  had  run  a  Mara- 
thon race. 

A  close  analogy  to  the  reflex  process  in  the  fighting 
of  animals  is  shown  in  the  role  played  by  the  sexual 
receptors  in  conjugation.  Adequate  stimulation  of 
these  two  distinct  groups  of  receptors,  the  noci  and 
the  sexual,  cause  specific  behavior,  —  the  one  toward 
embrace,  the  other  toward  repulsion.  Again,  one  of 
the  most  peremptory  causes  of  the  discharge  of 
energy  is  that  due  to  an  attempt  forcibly  to  obstruct 
the  mouth  and  the  nose,  threatening  asphyxia. 
Neither  friend  nor  foe  is  trusted,  and  a  desperate 
struggle  for  air  ensues.  It  will  be  readily  granted 
that  the  efforts  to  prevent  suffocation  were  established 
for  the  purpose  of  self-preservation,  but  the  discharge 
of  nerve-muscular  energy  to  this  particular  end  is  no 
more  specific  and  no  more  shows  adaptive  qualities 
than  do  the  preceding  examples.     Even  the  proposal 


to  bind  one  down  hand  and  foot  excites  resentment,  a 
feeling  of  self-preservation.  No  patient  views  with 
equanimity  the  application  of  shackles  preparatory  to 
anesthesia  for  an  operation. 

We  have  now  considered  some  of  the  causes  of  the 
discharge  of  nervous  energy  due  to  various  types  of 
harmful  physical  contact,  and  have  suggested  analo- 
gous though  antithetical  sexual  receptors.  The  re- 
sponse to  the  adequate  stimuli  of  each  of  the  several 
receptors  is  a  discharge  of  nerve  muscular  energy  of 
a  specific  type  :  One  type  for  the  ear,  one  for  the 
larynx,  one  for  the  pharynx,  another  for  the  nose, 
another  for  the  eye,  another  for  the  deep  ticklish 
points  of  the  chest  and  the  abdomen,  quite  another  for 
the  delicate  tickling  of  the  skin,  and  still  another  in 
response  to  sexual  and  to  painful  stimuli. 

According  to  Sherrington,  a  given  receptor  has  a 
low  threshold  for  only  one,  its  own  —  hence  a  specific 
stimulus  and  a  high  threshold  for  all  others  ;  that  is, 
the  doors  that  guard  the  nerve  paths  to  the  brain  are 
opened  only  on  receiving  the  proper  password. 
According  to  Sherrington's  law,  the  individual  as  a 
whole  responds  to  but  one  stimulus  at  a  time  ;  that  is, 
only  one  stimulus  occupies  the  nerve  paths  which  per- 
form acts,  i.e.,  the  final  common  path.  As  soon  as  a 
stronger  stimulus  reaches  the  brain  it  dispossesses 
whatever  other  stimulus  is  then  occupying  the  final 
common  path,  —  the  path  of  action.  The  various  re- 
ceptors have  a  definite  order  of  precedence  over  each 
other  (Sherrington).  For  example,  the  impulse  from 
the  delicate  ticklish  points  of  the  skin  whose  adequate 
stimulus  is  an  insect-like  contact  could  not  success- 
fully compete  for  the  final  common  path,  with  the 
stimulus  of  a  noci-ceptor.     The  stimulus  of  a  fly  on 

16 


the  nose  would  be  at  once  superseded  by  the  crushing 
of  a  finger.  In  quick  succession  do  the  various  re- 
ceptors (Sherrington)  occupy  the  final  common  path, 
but  each  stimulus  is  for  the  time  always  the  sole  pos- 
sessor, hence  the  nervous  system  is  integrated  (con- 
nected up)  to  act  as  a  whole.  Each  individual  at 
every  moment  of  its  life  has  a  limited  amount  of  dis- 
chargeable nervous  energy.  This  energy  is  at  the 
disposal  of  any  stimulus  that  obtains  possession  of  the 
final  common  path,  i.e.,  the  performance  of  acts.  Each 
discharge  of  energy  is  subtracted  from  the  sum  total, 
and  whether  the  subtractions  are  made  by  the  excita- 
tion of  noci-ceptors  by  trauma,  by  tickling,  by  fighting, 
by  fear,  by  flight  or  by  the  excitation  of  sexual  re- 
ceptors, singly  or  in  combination,  the  sum  total  of 
expenditure  of  energy,  if  large  enough,  produces 
exhaustion.  Apparently  there  is  no  distinction  be- 
tween that  state  of  exhaustion  which  is  due  to  the 
discharge  of  nervous  energy  in  response  to  trauma 
and  that  due  to  other  causes.  The  manner  of  the  dis- 
charge of  energy  is  specific  for  each  type  of  stimula- 
tion. On  this  conception  traumatic  shock  takes  its 
place  as  a  natural  phenomenon  and  is  divested  of  its 
mask  of  mystery. 

The  Discharge  of  Energy  Through  Stimulation  of  the 

Distance  Receiptors,  or  Through  Representation 

of  Injury  {Psychic) . 

We  will  now  turn  from  the  discussion  of  the  dis- 
charge of  nervous  energy  by  mechanical  stimuli  to  the 
discharge  of  energy  through  mental  perception. 
Phylogenetic  association  may  arise  through  the  distance 
receptors  as  well  as  through  physical  contact,  viz : 
through    sight,    hearing,     smell,     or     by    a    repre- 

17 


sentation  of  physical  experiences.  The  effect  upon 
the  organism  of  the  representation  of  injury  or  of  the 
perception  of  danger  through  the  distance  receptors  is 
designated  fear.  Fear  is  as  widely  distributed  in 
nature  as  is  its  cause,  that  is,  fear  is  as  widely  dis- 
tributed as  injury.  Animals  under  the  stimulus  of 
fear,  according  to  W.  T.  Hornaday,  not  only  may 
exhibit  preternatural  strength,  but  also  show  strategy 
of  the  highest  order,  a  strategy  not  seen  under  a  lesser 
stimulus.  In  some  animals  fear  is  so  intense  that  it 
defeats  escape  ;  this  is  especially  true  in  the  case  of 
birds  in  the  presence  of  snakes.  The  power  of  flight 
has  endowed  the  bird  with  an  easy  means  of  escape 
from  snakes,  especially  when  the  encounter  is  in  the 
tops  of  trees.  Here  the  snake  must  move  cautiously 
else  he  will  lose  his  equilibrium.  His  method  of 
attack  is  by  stealth.  When  the  snake  has  stalked  its 
prey,  the  bird  is  often  so  overcome  by  fear  that  it  can- 
not fly  and  so  becomes  an  easy  victim.  The  phe- 
nomena of  fear  are  described  by  Darwin  as  follows  : 

"  Fear  is  often  preceded  by  astonishment  and  is  so 
near  akin  to  it  that  both  lead  to  the  senses  of  sight  and 
hearing  being  instantly  aroused.  In  both  cases  the 
eyes  and  mouth  are  widely  opened  and  the  eyebrows 
raised.  The  frightened  man  at  first  stands  like  a 
statue,  motionless  and  breathless,  or  crouches  down  as 
if  instinctively  to  escape  observation.  The  heart  beats 
quickly  and  violently,  so  that  it  palpitates  or  knocks 
against  the  ribs.  That  the  skin  is  much  affected 
under  the  sense  of  fear,  we  see  in  the  marvelous  and 
inexplicable  manner  in  which  perspiration  immediately 
exudes  from  it.  This  exudation  is  all  the  more  re- 
markable as  the  surface  is  then  cold,  and  hence  the 

term,  '  a  cold  sweat '  ;  whereas  the  sudorific  glands 

18 


are  properly  excited  into  action  when  the  surface  is 
heated.  The  hairs  also  on  the  skin  stand  erect,  and 
the  superficial  muscles  shiver.  In  connection  with 
the  disturbed  action  of  the  heart,  the  breathing  is 
hurried.  The  salivary  glands  act  imperfectly  ;  the 
mouth  becomes  dry  and  is  often  opened  and  shut. 
I  have  also  noticed  that  under  slight  fear  there  is  a 
strong  tendency  to  yawn.  One  of  the  best  marked 
symptoms  is  the  trembling  of  all  the  muscles  of  the 
body,  and  this  is  often  first  seen  in  the  lips.  From  this 
cause,  and  from  the  dryness  of  the  mouth,  the  voice  be- 
comes husky  and  indistinct,  or  altogether  may  fail.  As 
fear  increases  into  agony  of  terror, we  behold,  as  under 
all  violent  emotions,  diversified  results.  The  heart  beats 
wildly,  or  may  fail  to  act,  and  faintness  ensue  ;  there 
is  a  death-like  pallor  ;  the  breathing  is  labored  ;  the 
wings  of  the  nostrils  are  dilated ;  there  is  a  gasping 
and  convulsive  motion  of  the  lips,  a  tremor  on  the 
hollowed  cheek,  a  gulping  and  catching  of  the  throat ; 
the  uncovered  and  protruding  eyeballs  are  fixed  on  the 
object  of  terror,  or  they  may  roll  restlessly  from  side 
to  side.  The  pupils  are  said  to  be  enormously  dilated. 
All  the  muscles  of  the  body  become  rigid,  or  may  be 
thrown  into  convulsive  movements.  The  hands  are 
alternately  clenched  and  opened,  often  with  a  twitch- 
ing movement.  The  arms  may  be  protruded,  as  if 
they  were  to  avert  some  dreadful  danger,  or  may  be 
thrown  wildly  over  the  head.  In  other  cases  there  is  a 
sudden  and  uncontrollable  tendency  to  headlong  flight ; 
and  so  strong  is  this,  that  the  boldest  soldier  may  be 
seized  with  a  sudden  panic.  As  fear  arises  to  an 
extreme  pitch,  the  dreadful  scream  of  terror  is  heard. 
Great  beads  of  sweat  stand  on  the  skin.  All  the 
muscles  of  the  body  are  relaxed.     Utter  prostration 

*9 


soon  follows,  and  the  mental  powers  fail.  The  intes- 
tines are  affected.  The  sphincter  muscles  cease  to 
act  and  no  longer  retain  the  contents  of  the  body. 
Men  during  numberless  generations  have  endeavored 
to  escape  from  their  enemies  or  danger  by  headlong 
flight,  or  by  violently  struggling  with  them  ;  and  such 
great  exertions  will  have  caused  the  heart  to  beat 
violently,  the  breathing  to  be  hurried,  and  the  chest 
to  heave,  and  the  nostrils  to  be  dilated.  As  these  ex- 
ertions have  often  been  prolonged  to  the  last  extremity, 
the  final  result  will  have  been  utter  prostration,  pallor, 
perspiration,  trembling  of  all  the  muscles,  or  their 
complete  relaxation.  And  now,  whenever  the  emo- 
tion of  fear  is  strongly  felt,  though  it  may  not  be  from 
any  exertion,  the  same  results  tend  to  reappear, 
through  the  force  of  inheritance  and  association." 
(Danvin.) 

In  an  experimental  research,  we  found  evidence 
that  the  physiologic  phenomena  of  /ewhave  a  physical 
basis.  This  evidence  is  morphologic  alterations  in  the 
brain  cells,  similar  to  certain  stages  of  surgical  shock 
and  in  fatigue  from  muscular  exertion.  For  the  pres- 
ent we  will  assume  that  fear  is  a  representation  of 
trauma.  Because  fear  was  created  by  trauma,  fear 
causes  a  discharge  of  the  energy  of  the  nervous  system 
on  the  law  of  phylogenetic  association.  The  almost 
universal  fear  of  snakes,  of  blood  and  of  death  and 
dead  bodies,  may  have  such  a  phylogenetic  origin.  It 
was  previously  stated  that  under  the  stimulus  of  fear 
animals  show  preternatural  strength.  An  analysis 
of  the  phenomena  of  fear  shows  that,  so  far  as  can 
be  determined,  all  of  the  functions  of  the  body  re- 
quiring the  expenditure  of  energv  and  which  are  of 
no  direct  assistance  in  the  effort  toward  self-preser- 

20 


vation  are  suspended.  In  voluntary  expenditure  of 
muscular  energy,  such  as  in  the  chase,  the  suspension 
of  other  functions  is  by  no  means  so  complete.  Fear, 
hence  trauma,  may,  therefore,  drain  to  the  last  dreg 
the  dischargeable  nervous  energy ;  therefore,  the 
greatest  possible  exhaustion  may  be  produced  by  fear 
and  trauma.  This  is  a  distinction  between  fear  and 
desire. 

There  is  a  factor,  however,  that  influences  the  dis- 
charge of  energy  which  I  must  discuss  briefly.  I 
refer  to  summation. 

Summation. 

In  the  discharge  of  energy,  summation  plays  an 
important  role.  Summation  is  attained  by  the  repeti- 
tion of  stimuli  at  such  a  rate  that  each  succeeding  stim- 
ulus is  applied  before  the  nerve  cells  have  returned  to 
the  resting  stage  from  the  preceding  stimulus.  If 
drops  of  water  fall  upon  the  skin  from  a  sufficient  height 
to  cause  the  slightest  unpleasant  sensation,  and  at  such 
a  rate  that  before  the  effect  of  the  stimulus  of  one  drop 
has  passed  another  drop  falls  in  precisely  the  same 
spot,  there  will  be  felt  a  gradually  increasing  painful 
sensation  until  it  becomes  unbearable.  This  is  sum- 
mation. When  a  patient  requires  for  a  long  time 
frequent  painful  wound  dressings,  there  is  a  gradual 
increase  in  the  acuteness  of  the  pain  receptors.  This 
is  summation.  In  a  larger  sense  the  behavior  of  the 
entire  individual  gives  considerable  evidence  of  sum- 
mation, e.g.,  in  the  training  of  athletes  the  rhythmic 
discharge  of  muscular  energy  at  such  intervals  that 
the  resting  stage  is  not  reached  before  a  new  exercise 
is  given  results  in  a  gradual  ascent  in  efficiency  until 
the  maximum  is  reached.      This  is  summation,  and 


summation  plays  a  large  role  in  the  development  of 
both  normal  and  pathologic  phenomena. 

We  have  now  pointed  out  the  manner  in  which  at 
least  a  part  of  nervous  energy  of  man  may  be  dis- 
charged. The  integrative  action  of  the  nervous  system 
and  the  discharge  of  nervous  energy  by  phylogenetic 
association  may  be  illustrated  by  the  analogy  of  an 
electric  automobile.  The  electric  automobile  is  com- 
posed of  three  principal  parts  :  the  motor  and  the 
wheels  (the  muscular  system  and  the  skeleton)  ;  the 
cells  of  the  battery  containing  stored  electricity  (brain 
cells,  nervous  energy)  ;  and  the  controller  which  is 
connected  with  the  cells  by  wiring  (the  receptors  and 
the  nerve  fibers)  ;  and  an  accelerator  button  for  in- 
creasing the  electrical  discharge  (thyroid  gland  ?  ) . 
The  machine  is  so  constructed  that  it  acts  as  a  whole 
for  the  accomplishment  of  a  single  purpose.  When 
the  controller  is  adjusted  for  going  ahead  (adequate 
stimulus  of  a  receptor) ,  then  the  conducting  paths  (the 
final  common  path)  for  the  accomplishment  of  that  pur- 
pose are  all  open  to  the  flow  of  the  current  from  the 
battery,  and  the  vehicle  is  integrated  to  go  ahead.  It 
spends  its  energy  to  that  end  and  is  closed  to  all  other 
impulses.  When  the  controller  is  set  for  reverse,  the 
machine  is  by  this  adequate  stimulus  integrated  to 
back,  and  the  battery  is  closed  to  all  other  impulses. 
Whether  integrated  for  going  forward  or  backward,  if 
the  battery  be  discharged  at  a  proper  rate  until  ex- 
hausted, the  cells,  though  possessing  no  more  power 
(fatigue),  have  sustained  no  further  impairment  of 
their  elements  than  that  of  normal  wear  and  tear. 
Furthermore,  they  may  be  restored  to  normal  activity 
by  recharging  (rest) .  If  the  vehicle  be  placed  against 
a  stone  wall,  and  the  controller  be  placed  at  top  speed 


ahead  (trauma  and  fear) ,  and  if  the  accelerator  is  on 
as  well  (thyroid  secretion?),  though  the  machine  will 
not  move,  the  battery  will  not  only  soon  be  exhausted, 
but  the  battery  elements  themselves  will  be  seriously 
damaged  (exhaustion,  —  surgical  shock). 

We  have  now  presented  some  evidence  that  nerv- 
ous energy  is  discharged  by  the  adequate  stimulation 
of  one  or  more  of  the  various  receptors  that  have  been 
developed  in  the  course  of  evolution.  In  response  to 
an  adequate  stimulus,  the  nervous  system  is  integrated 
for  the  specific  purpose  of  the  stimulated  receptor,  and 
but  one  stimulus  at  a  time  has  possession  of  the  final 
common  path, —  the  nerve  mechanisms  for  action. 
The  most  numerous  receptors  are  those  for  harmful 
contact.  These  are  the  noci-ceptors.  The  effect  of 
the  adequate  stimulus  of  a  noci-ceptor  is  like  that  of 
pressing  an  electric  button  that  sets  in  motion  great 
machinery. 

With  this  conception,  the  human  body  is  likened  to 
a  musical  instrument, —  an  organ,  the  keyboard  of 
which  is  composed  of  the  various  receptors  upon 
which  environment  plays  the  many  tunes  of  life  ;  and 
written  within  ourselves  in  symbolic  language  is  the 
history  of  our  evolution.  The  skin  may  be  the  "  Ro- 
setta  Stone  "  which  furnishes  the  key. 

Anoci- Association . 

We  are  now  prepared  on  the  law  of  phylogenetic 
association  to  make  a  practical  application  of  the 
principles  of  the  discharge  of  nervous  energy.  In 
the  case  of  a  surgical  operation,  if  fear  be  excluded 
and  if  the  nerve  paths  between  the  field  of  operation 
and  the  brain  be  blocked  with  cocaine,  there  will  be  no 
discharge  of  energv  due  to  the  operation;  hence,  there 

23 


can  be  no  shock,  no  exhaustion.  Under  these  condi- 
tions of  operation  the  nervous  system  is  protected 
against  noci-association  whether  by  noci-perception  or 
by  an  adequate  stimulation  of  noci-ceptors.  The 
state  of  the  patient  in  whom  all  noci-associations  are 
excluded  can  be  described  only  by  coming  a  new 
word.      That  word  is  "  anon- association.'''' 

The  difference  between  anesthesia  and  anoci-asso- 
ciation  is  that  although  inhalation  anesthesia  confers  the 
beneficent  loss  of  consciousness  and  freedom  from 
pain,  it  does  not  prevent  the  nerve  impulses  from 
reaching  and  influencing  the  brain,  and  hence  does 
not  prevent  surgical  shock  nor  the  train  of  later  nerv- 
ous impairments  so  well  described  by  Mumford. 
Anoci- association  excludes  fear.  pain,  shock  and  post- 
operative neuroses.  Anoci-association  is  accomplished 
bv  a  combination  of  special  management  of  patients 
(applied  psychology),  morphine,  inhalation  anesthe- 
sia and  local  anesthesia. 

We  have  now  presented  in  summary  much  of  the 
mass  of  experimental  and  clinical  evidence  we  have 
accumulated  in  support  of  our  principal  theme,  viz  : 
that  the  discharge  of  nervous  energy  is  accomplished 
bv  the  law  of  phvlogenetic  association.  If  this  point 
seems  to  have  been  labored,  it  is  because  we  expect 
to  rear  upon  this  foundation  a  clinical  structure.  How 
does  this  hvpothesis  apply  to  surgical  operations  ? 

Prevention  of  Shock  by  the  Application  of  the  Principle 
of  Anoci- Association. 

Upon  this  hypothesis  a  new  principle  in  operative 
surgery  is  founded,  viz  :  operation  during  the  state  of 
anoci-association.      Assuming    there   is   no   unfavorable 

-4 


effect  of  the  anesthetic,  and  no  hemorrhage,  the  nerve 
cells  of  the  brain  cannot  be  exhausted  in  the  course  of 
a  surgical  operation  except  by  fear,  or  trauma,  or  by 
both.  Fear  mav  be  excluded  by  narcotics  and  spe- 
cial consideration  until  the  patient  is  rendered  uncon- 
scious bv  inhalation  anesthesia.  Then  in  addition  to 
inhalation  anesthesia,  blocking  with  cocaine  the  nerve 
paths  between  the  brain  and  the  field  of  operation  will 
place  the  patient  in  the  beneficent  state  of  anoci-asso- 
ciation,  and  at  the  completion  of  the  operation  the  pa- 
tient will  be  as  free  from  shock  as  at  the  beginning. 
In  so-called  '*  fair  risks  such  precautions  mav  not 
be  necessary,  but  in  cases  handicapped  bv  infections, 
by  anemia,  by  previous  shock  and  by  Graves'  disease, 
etc..  anoci-association   mav  become  vitally  important. 

Graves   Disease. 

Applying  the  principle  of  the  discharge  of  nervous 
energy  bv  phylogenetic  association,  and  on  the  addi- 
tional hypothesis  that  in  the  discharge  of  nervous 
energy  the  thvroid  gland  is.  through  the  nervous  sys- 
tem, stimulated,  we  can  explain  many  phenomena  of 
Graves'  disease  and  possibly  supply  some  of  the  factors 
to  explain  both  the  genesis  and  the  cure  of  the  disease. 

In  the  wild  state  of  animal  life  in  which  only  the 
fittest  survive  in  the  struggle  for  existence,  every 
point  of  advantage  mav  have  selection  value.  An  an- 
imal engaged  in  battle  or  in  a  desperate  effort  at  es- 
cape will  be  able  to  give  a  better  account  of  itself  if 
it  has  some  means  of  accelerating  the  discharge  of 
energy,  some  influence  like  that  of  oil  upon  the  kin- 
dling fire.  There  is  evidence,  though  perhaps  not 
conclusive,  that  such  an  influence  is  exerted  by  the 
thvroid  °;land.    This  evidence  is  as  follows  :   In  mvxe- 


dema,  a  condition  characterized  by  a  lack  of  thyroid 
secretion,  there  is  a  dulness  of  reflexes,  and  of  intel- 
lect, a  lowered  muscular  power,  and  generally  a 
sluggish  discharge  of  energy.  In  Graves'  disease 
there  is  an  excessive  production  of  thyroid  secretion. 
In  this  disease  the  reflexes  are  greatly  sharpened, 
energy  is  discharged  with  very  greatly  increased  facil- 
ity, and  metabolism  is  at  a  maximum.  The  same 
holds  true  in  the  administration  of  thyroid  extract  in 
large  doses  in  normal  subjects.  In  the  course  of 
sexual  activities  there  is  an  increased  action  of  the 
thyroid  as  indicated  by  an  increased  size  and  vascu- 
larity of  the  thyroid.  In  fear  and  in  injury  in  cases 
of  Graves'  disease  the  thyroid  is  probably  stimulated  to 
increased  activity  as  indicated  by  the  increased  activity 
of  the  thyroid  circulation,  by  an  increase  in  the  size  of 
the  gland,  by  presenting  the  histologic  appearance  of 
activity  in  the  nucleus  of  the  cells,  and  by  an  increase 
of  the  toxic  symptoms.  Finally,  Asher  has  stated 
that  electric  stimulation  of  the  nerve  supply  of  the 
thyroid  causes  an  increased  secretion.  The  origin  of 
many  cases  of  Graves'  disease  is  closely  associated 
with  some  of  the  causes  of  the  discharge  of  nervous 
energy,  especially  depressive  influences,  such  as  nerv- 
ous shocks,  worry  and  nervous  strain,  disappointment 
in  love,  business  reverses,  illness  and  death  of  rela- 
tives and  friends.  The  association  of  activity  of  the 
thyroid  with  procreation  is  well  known,  hence  the  in- 
cidence of  the  double  strain  of  overwork  or  of  fear 
and  the  sexual  evolution  in  maturing  girls  is  obviously 
favorable  to  the  development  of  Graves'  disease. 
The  presence  of  a  colloid  goiter  is  a  suitable  soil  for 
the  development  of  Graves'  disease.  I  fully  recog- 
nize the  evidence   that   infection   or   auto-intoxication 

26 


may  be  contributing   factors  and  must  be  assigned 
their  role. 

I  have  never  known  a  case  of  Graves'  disease  to 
develop  from  success  or  from  happiness  alone,  nor 
from  hard  physical  labor,  unattended  by  strain,  nor 
from  the  results  of  energy  voluntarily  discharged. 
Some  cases  seem  to  have  had  their  origin  in  over-do- 
sage of  thyroid  extract  in  too  vigorous  an  attempt  to 
cure  a  colloid  goiter.  In  Graves'  disease  one  of  the 
most  striking  characteristics  is  the  patient's  loss  of 
control  and  an  increased  susceptibility  to  stimuli,  espe- 
cially to  trauma  and  to  fear  and  to  the  administration 
of  thyroid  extract.  It  has  been  shown  that  the  vari- 
ous causes  of  the  discharge  of  nervous  energy  produce 
alterations  in  the  nervous  system  and  probably  in  the 
thyroid  gland.  This  is  especially  true  of  the  fear 
stimulus.  This  is  clearly  demonstrated  in  the  brains 
of  rabbits  subjected  to  fear  alone.  Of  special  interest 
is  the  effect  of  daily  fright.  In  this  case  the  brain 
cells  show  a  distinct  change,  although  the  animal  is 
subjected  to  no  fear  for  twenty-four  hours  before  it  is 
killed.  Now,  a  great  distinction  between  man  and 
the  lower  animals  is  the  greater  control  man  has  ac- 
quired over  his  actions.  This  quality  of  control,  hav- 
ing been  phylogenetically  most  recently  acquired,  is 
the  most  vulnerable  to  various  nocuous  influences. 
The  result  of  a  constant  noci-integration  may  be  a 
wearing  out  of  the  control  cells  of  the  brain.  In 
Graves'  disease  there  has  been  demonstrated  in  a 
typical  case  a  marked  morphologic  change  in  the 
brain  cells.  As  previously  stated,  the  origin  of  many 
cases  of  Graves'  disease  is  associated  in  a  broad  sense 
with  some  noci-influence.  If  this  influence  causes 
stimulation  of  both  the  brain  and  the  thyroid,  its  ex- 

27 


cessive  action  may  cause  impairment  of  the  brain  and 
hyperplasia  of  the  thyroid  as  well.  As  self-control  is 
impaired,  fear  obtains  ascendency  and,  pari  passu, 
would  stimulate  the  thyroid  still  more  actively.  Finally, 
the  fear  of  the  disease  itself  becomes  a  noci-stimulus. 
As  the  thyroid  secretion  causes  an  increase  in  the 
facility  for  the  discharge  of  nervous  energy,  there  is 
established  a  pathologic  reciprocal  interaction  between 
the  brain  and  the  thyroid.  The  effect  of  the  con- 
stantly recurring  stimulus  of  the  noci-influence  is 
heightened  by  summation.  This  reciprocal  goading 
may  continue  until  either  the  brain  or  the  thyroid  is 
destroyed.  If  the  original  noci-stimulus  is  withdrawn 
before  the  fear  of  the  disease  becomes  too  strong,  and 
before  too  much  injury  to  the  brain  and  the  thyroid 
has  been  inflicted,  a  spontaneous  cure  may  result. 
Cure  may  be  greatly  facilitated  by  a  complete  rest  cure. 
A  cure  implies  the  return  of  the  brain  cells  to  their 
normal  state,  with  the  re-establishment  of  the  normal 
self-control,  and  the  restoration  of  the  thyroid  to  its 
normal  state.  Then  the  impulses  of  daily  life  will 
once  more  have  possession  of  the  final  common  path 
and  the  noci-influence  be  dispossessed.  The  discov- 
ery of  the  real  cause  of  a  given  case  of  Graves'  dis- 
ease is  frequently  difficult  because  the  exciting  cause 
may  be  personal  and  is  "painful.  Of  extreme  interest 
is  the  fact  that  the  patient  in  the  acute  stage  may  be 
unable  to  refer  to  the  real  cause  without  exhibiting  an 
exacerbation  of  the  symptoms  of  the  disease.  I  pre- 
sume no  case  should  be  regarded  as  cured  until  refer- 
ence can  be  made  to  the  cause  without  an  abnormal 
reaction.  It  has  been  established  that  in  Graves'  dis- 
ease injury  to  any  part  of  the  body  even  under  inhala- 
tion anesthesia  causes  an  exacerbation  of  the  disease. 

28 


Fear  alone  may  cause  an  acute  exacerbation.  These 
acute  exacerbations  are  frequently  designated  "  hyper- 
thyroidism "  and  are  the  special  hazard  of  operation. 

In  operating  on  subjects  of  Graves'  disease  on  the 
principle  of  anoci-association,  there  is  scarcely  a  change 
in  the  pulse,  in  the  respiration  or  in  the  nervous  state 
at  the  close  of  the  operation.  Against  the  effect  of 
the  inflowing  stimuli  from  the  wound  after  the  cocaine 
has  worn  off  I  know  no  remedy.  It  is  necessary, 
therefore,  in  the  serious  cases  not  to  venture  too  far. 
Since  the  adoption  of  this  new  method  (anoci-associa- 
tion) my  operative  results  have  been  so  vastly  improved 
that  I  now  regard  no  case  of  Graves'  disease  as  in- 
operable, at  least  to  the  extent  of  making  a  double 
ligation. 

If  we  believe  that  a  continuous  stimulation  of  both 
the  brain  and  the  thyroid  gland,  on  the  law  of  phylo- 
genetic  association,  accelerated  by  summation,  plays  a 
role  in  the  establishment  of  the  pathologic  interaction 
seen  in  Graves'  disease,  then  it  is  but  the  next  step  to 
assume  that  if  the  nerve  connection  between  the  brain 
and  the  thyroid  is  severed,  or  if  the  lobe  is  excised 
and  the  patient  is  reinforced  by  a  sojourn  in  a  sanato- 
rium, or  some  environment  free  from  former  noci-asso- 
ciation,  the  patient  will,  providing  the  brain  cells, 
the  heart  or  other  essential  organs  have  not  suffered 
irreparable  damage,  be  restored  to  normal  health. 
There  are  still  many  missing  links,  and  the  foregoing 
is  not  offered  as  a  final  solution,  although  many  of  the 
phenomena  from  the  view-point  of  the  surgeon  are 

explicable. 

Sexual  JVeur asthenia. 

The  state  of  sexual  neurasthenia  is  in  many  re- 
spects analogous  to  that  of  Graves'  disease.     In  the 

29 


sexual  reflexes  summation  leads  to  hyper-excitability 
to  psychic  and  mechanical  stimuli  of  a  specific  tvpe 
analogous  to  the  hyper-excitability  in  Graves'  disease 
to  trauma  and  fear  ;  both  are  based  on  the  law  of  the 
discharge  of  energy  by  phylogenetic  association  and 
summation.  It  would  be  interesting  to  observe  the 
effect  of  interrupting  the  nerve  impulses  from  the  field 
of  the  sexual  receptors  by  injections  of  alcohol  or  other 
agencies  and  thus  exclude  the  associational  stimuli 
until  the  nervous  mechanism  has  again  become  re- 
stored to  the  normal. 

Interpretation  of  Some  of  the  Phenomena  of  Certain 

Diseases  of  the  Abdomen  on  the  Hypothesis  of 

Phylogenetic  Association. 

On  the  law  of  phylogenetic  association,  it  is  prob- 
able that  many  of  the  phenomena  of  certain  lesions  in 
the  abdominal  cavity  become  explicable.  The  noci- 
ceptors in  the  abdomen,  like  noci-ceptors  elsewhere, 
have  been  established  by  some  kind  of  injury  to  which 
this  region  has  been  frequently  exposed  over  vast 
periods  of  time.  On  this  premise,  we  could  at  once 
predict  that  there  are  no  noci-ceptors  for  heat  within 
the  abdomen  because  during  countless  years  the  in- 
tra-abdominal region  has  not  come  in  contact  with 
heat.  That  this  inference  is  correct  is  shown  by  the 
fact  that  the  application  of  a  thermocautery  to  the  in- 
testines when  completing  a  colostomy  in  a  conscious 
patient  is  absolutely  painless.  One  could  also  pre- 
dict the  fact  that  there  are  no  touch  receptors  in  the 
abdominal  viscera,  hence  no  sense  of  touch  in  the 
peritoneum.  Just  as  the  larynx,  the  ear,  the  nose, 
the  sole  of  the  foot  and  the  skin  have  all  developed 
the  specific  type  of  noci-ceptors  which  are  adapted 

30 


for  their  specific  protective  purposes,  and  when  ade- 
quately stimulated  respond  in  a  specific  manner  on 
the  law  of  phylogenetic  association,  so  the  abdominal 
viscera  have  developed  equally  specific  noci-ceptors  as 
a  protection  against  specific  nocuous  influences.  The 
principal  harmful  influences  to  which  the  abdominal 
viscera  may  have  been  long  exposed  are  deep  tearing 
injuries  by  teeth  and  claws  in  the  course  of  the  in- 
numerable struggles  of  our  progenitors  with  each 
other  and  with  their  enemies  ;  the  perforation  of  the 
intestinal  tract  from  ulcers,  injuries,  appendicitis, 
gallstones,  etc.,  causing  peritonitis  ;  and  over-disten- 
tion  of  the  hollow  viscera  from  various  forms  of  ob- 
struction. Whatever  may  be  the  connection,  it  is  a 
fact  that  the  type  of  trauma  from  fighting  corresponds 
nicely  to  that  which  in  the  experimental  laboratory 
causes  the  most  shock.  Division  of  the  intestines 
with  a  sharp  knife  causes  no  pain,  but  pulling  on  the 
mesentery  elicits  pain.  Likewise,  ligature  of  the 
stump  of  the  appendix  causes  sharp  cramp-like  pains. 
Sharp  division  of  the  gall  bladder  causes  no  pain,  but 
distention,  which  is  the  gall  bladder's  most  common 
pathologic  state,  produces  pain.  Distention  of  the 
intestines  causes  great  pain,  but  sharp  cutting  or 
burning  causes  none.  In  the  abdominal  viscera,  like 
the  superficial  parts,  noci-ceptors  have  been  pre- 
sumedly developed  by  specific  harmful  influences,  and 
each  noci-ceptor  is  open  to  stimulation  only  by  the 
particular  type  that  produced  it. 

As  we  have  just  stated,  pain  is  associated  with  the 
excitation  of  noci-ceptors,  and  these  may  take  prece- 
dence over  and  dispossess  the  routine  functions,  such 
as  peristalsis,  secretion  and  absorption,  of  their  occu- 
pancy of  their  respective  nervous  mechanisms,  just  as 

31 


fear  does.  Hence,  the  loss  of  weight,  the  lassitude, 
the  indigestion,  the  constipation  and  the  many  altera- 
tions in  the  function  of  the  various  glands  and  organs 
of  the  digestive  system  in  chronic  appendicitis,  chronic 
gall-bladder  disease,  may  be  explained.  This  hy- 
pothesis readily  explains  the  extraordinary  improve- 
ment in  the  digestive  functions  and  the  general  health 
following  the  removal  of  an  appendix  so  slightly  al- 
tered physically  that  only  the  clinical  results  in  many 
cases  could  persuade  one  that  this  change  could  be  an 
adequate  cause  for  such  far-reaching  and  important 
symptoms.  It  would  equally  explain  certain  gall- 
bladder phenomena  —  the  indigestion,  loss  of  weight, 
disturbed  functions,  etc.  This  hypothesis  may  supply 
the  explanation  of  the  disturbance  from  an  active  anal 
fissure,  which  is  a  potent  noci-associator,  and  the  con- 
sequent disproportionate  relief  after  the  trivial  opera- 
tion for  its  cure.  Noci-association  would  well  explain 
the  great  functional  disturbances  of  the  viscera  imme- 
diately following  abdominal  operations. 

Post-operative  and  traumatic  neuroses  are  at  once 
explained  on  the  ground  of  noci-association,  with  the 
resulting  strain  upon  the  brain  cells,  causing  in  them 
physical  lesions.  If  one  were  placed  against  a  wall 
and  were  looking  into  the  gun  muzzles  of  a  squad  of 
soldiers  and  were  told  that  he  must  not  be  afraid  be- 
cause in  nine  chances  out  of  ten  he  would  not  be 
killed  outright  when  the  volley  was  fired,  would  it 
help  him  to  be  told  that  he  must  not  be  afraid "?  Such 
an  experience  would  be  written  indelibly  on  his  brain. 
Yet  this  is  much  the  same  position  in  which  some 
surgical  patients  are  placed.  In  railway  wrecks  we 
can  readily  understand  the  striking  difference  between 
the  conscious  passenger  and  the  sleeping  or  drunken 

32 


one.  In  the  latter  persons  the  noci-ceptors  and  re- 
ceptors were  not  aroused,  hence  their  immunity.  In 
the  functional  disturbances  of  the  pelvic  organs  asso- 
ciation and  summation  may  play  a  large  role.  On 
this  hypothesis  many  cases  of  neurasthenia  may  well 
be  explained.  In  the  behavior  of  the  individual  as  a 
whole  summation  may  well  be  a  scientific  expression 
for  "nagging."  Many  other  pathologic  phenomena 
may  be  explained  in  a  similar  manner.  Thus  we  can 
better  understand  the  variation  of  a  gastric  analysis  in 
a  timid  patient  alarmed  over  his  condition  and  afraid 
of  the  hospital.  He  is  integrated  by  fear,  and  fear 
taking  precedence  over  all  other  impulses,  no  organ 
functionates  normally.  On  the  same  ground,  one  sees 
animals  in  captivity  pine  away  under  the  dominance 
of  fear.  The  exposure  of  a  sensitive  brain  to  the 
naked  possibility  of  death  from  a  surgical  operation  is 
equal  to  uncovering  a  photographic  plate  in  the  bright 
sunlight  to  inspect  it  before  putting  it  in  the  camera. 
This  principle  explains,  too,  the  physical  influence  of 
the  physician  or  surgeon  who,  by  his  personality,  in- 
spires, like  a  Kocher,  absolute  confidence  in  his 
patient.  The  brain  through  its  power  of  phylogenetic 
association  controls  many  processes  that  have  wholly 
escaped  from  the  notice  of  the  "  practical  man."  It 
is  on  the  law  of  association  that  a  flower,  a  word,  a 
touch,  a  cool  breeze,  or  even  the  thought  of  a  fishing 
rod  or  of  a  gun,  are  helpful.  On  the  contrary,  any 
fragment  of  associational  evidence  of  despair  or  mis- 
fortune, whether  it  be  the  corrugated  brow,  the 
gloomy  silence  of  despair,  a  doubtful  word,  is  equally 
depressing,  and  so  could  one  add  indefinitely  to  the 
symbolism  that  governs  our  daily  lives.  Thus,  we 
see  that  through  the  law  of  inheritance  and  noci-asso- 

33 


ciation,   we    are   able    to  read    into   the    behavior  of 
various  diseases  a  new  meaning. 

Observations  on  Patients  Whose  Associational  Centers 

Are  Dulled,  and  on  Diseases  and  Injuries  of 

Regions  not  Endowed  with  JVoci-ceptors. 

Reversing  the  order,  let  us  glance  at  the  patient 
who  is  unconscious  and  who,  therefore,  has  lost  much 
of  the  power  of  association.  His  mouth  is  usually 
dry,  the  digestive  processes  are  at  a  low  ebb,  the 
aroma  of  food  causes  no  secretion  of  saliva.  Tickling 
the  nose  causes  no  sneezing ;  he  catches  no  cold. 
The  laryngeal  reflex  is  lost  and  food  may  be  quietly 
inhaled.  The  entire  process  of  metabolism  is  low. 
The  contrast  between  man  with  associational  centers 
keen  and  man  with  these  centers  dulled  or  lost  is  the 
contrast  between  life  and  death.  On  the  behavior  of 
the  individual  without  associational  power  much  might 
be  said. 

On  the  laws  of  adaptation  through  natural  selection, 
phylogeny  and  association,  one  should  expect  no  pain 
in  abscess  of  the  brain,  in  abscess  of  the  liver,  in 
pylephlebitis,  in  infection  of  the  hepatic  vessels,  in 
endocarditis.  This  law  explains  why  there  are  no 
noci-ceptors  for  cancer,  and  active  noci-ceptors  for  the 
acute  infections,  because  against  cancer  nature  has  no 
helpful  response  to  offer  and  in  certain  of  the  acute 
pyogenic  infections  the  noci-ceptors  give  the  benefi- 
cent physiologic  rest. 

Could  we  dispossess  ourselves  of  the  shackles  of 
psychology,  and  forget  its  confusing  nomenclature, 
and  view  the  human  brain,  as  Sherrington  has  said, 
"  as  the  organ  of,  and  for,  the  adaptation  of  nervous 
reaction,"  many  clinical  phenomena  would  appear  in 
a  clearer  light. 

34 


Natural  Selection   and    Chemical  JVoci-association    in 
the  Infections. 

Heretofore  we  have  considered  the  behavior  of  the 
individual  as  a  whole  in  response  to  a  certain  type  of 
noci-influences.  We  have  been  thinking  in  terms  of 
physical  escape  from  gross  physical  dangers,  or  grap- 
pling with  gross  nerve-muscular  enemies  of  the  same 
or  of  other  species,  as  related  to  some  problems  in 
medicine.  To  explain  these  phenomena  we  have 
invoked  the  aid  of  the  laws  of  natural  selection  and 
phylogenetic  association.  If  our  conclusions  are  cor- 
rect, then  it  should  follow  that  in  the  same  laws  we 
can  find  the  explanation  of  immunity,  which,  of 
course,  means  a  defensive  response  to  our  microscopic 
enemies.  There  should  be  no  more  difficulty  in 
building  up  by  natural  selection  an  efficient  army  of 
phagocytes,  or  specific  chemical  reactions  against 
microscopic  enemies,  than  the  building  up  of  the  various 
noci-ceptors  for  our  muscular  defense  against  our 
gross  enemies.  That  immunity  is  a  chemical  reaction 
is  no  hindrance  to  the  application  of  the  law  of  natural 
selection  nor  of  association.  What  essential  differ- 
ence is  there  between  the  chemical  defense  of  the 
skunk  against  its  nerve-muscular  enemies  and  its 
chemical  defense  (immunity)  against  its  microscopic 
enemies  ? 

The  administration  of  vaccines  becomes  the  ade- 
quate stimuli  by  phylogenetic  association  of  a  chem- 
ical nature  whereby  immune  bodies  are  produced. 

While  mentioning  this  subject  I  will  only  raise  the 
question  whether  or  not  the  specific  character  of  the 
inaugural  symptoms  of  some  infectious  diseases  may 
not  be  due  to  phylogenetic  association.  These  in- 
augural symptoms  are  measurably  a  recapitulation  of 

35 


the  leading  phenomena  of  the  disease  in  its  completed 
clinical  picture.  Thus  the  furious  immediate  phe- 
nomena of  pneumonia,  of  peritonitis,  of  erysipelas,  of 
the  exanthemata,  show  phenomena  of  exaggeration 
which  are  analogous  to  the  phenomena  of  physical 
injury  and  of  fear  of  physical  violence.  Just  as  the 
acute  phenomena  of  fear  or  the  adequate  stimulus  of 
noci-ceptors  are  a  recapitulation  of  phylogenetic 
struggles,  so  may  the  inaugural  symptoms  of  infec- 
tions be  a  similar  phylogenetic  recapitulation  of  the 
course  of  the  disease.  A  certain  amount  of  negative 
evidence  is  supplied  by  the  difference  between  the 
response  of  a  dose  of  toxins  as  compared  with  a  dose 
of  a  standard  drug.  No  drug  in  therapeutic  dosage 
except  the  iodine  compounds  causes  a  febrile  re- 
sponse ;  no  drug  causes  a  chill ;  all  specific  toxins  cause 
febrile  responses,  and  many  cause  chills.  If  a  species 
of  animal  had  been  poisoned  by  a  drug  over  vast 
periods  of  time,  and  if  natural  selection  had  success- 
fully established  a  self-defensive  response,  then  the 
administration  of  that  drug  would  cause  the  noci- 
association  (chemical) ,  and  a  specific  reaction  analo- 
gous to  that  following  Coley's  toxins  might  be 
expected.  Bacterial  noci-association  probably  operates 
through  the  same  law  as  the  physical  contact  of  en- 
vironment does.  But  natural  selection  is  impartial. 
It  must  be  supposed  that  it  acts  upon  the  microscopic 
invader  just  as  well  as  upon  the  host.  On  this 
ground  one  would  infer  that  the  bacteria  of  acute  in- 
fections must  have  met  by  natural  selection  each  ad- 
vance of  the  immunity  of  the  host  by  the  same  law  of 
natural  selection.  Hence,  the  fast  and  furious  strug- 
gle between  man  and  his  microscopic  enemies  merely 
indicates    to  what    extent   natural   selection    has    de- 

36 


veloped  the  attack  and  the  defense  respectively.  This 
is  analogous  to  the  quick  and  decisive  battles  of  the 
carnivora  when  fighting  among  themselves  or  when 
contending  against  their  ancient  enemies.  But  when 
phylogenetically  strange  animals  meet  each  other, 
they  do  not  understand  how  to  conduct  a  fight. 
Natural  selection  has  not  had  the  opportunity  of 
teaching  them.  The  acute  infections  have  the  char- 
acteristics of  being  ancient  enemies.  On  this  hypoth- 
esis one  might  understand  the  high  mortality  of 
measles  when  introduced  into  a  new  country.  The 
infecting  agency  of  measles  by  natural  selection  has 
become  a  powerful  enemy  of  the  human  race,  but  the 
particular  race  to  whom  this  infection  is  newly  intro- 
duced has  not  had  the  equal  advantage  of  building  up 
its  defense  by  the  same  law  —  natural  selection.  The 
variation  in  the  effect  of  auto-  and  iso-pollution  of 
water  may  be  explained  in  a  similar  manner.  Im- 
munity and  food  assimilation  are,  therefore,  on  equal 
footing.  May  not  the  phenomena  of  anaphylaxis  be 
studied  on  associational  lines  ?  Then,  too,  there  may- 
be chemical  noci-associations  of  enemies  now  extinct, 
which  like  the  ticklish  points  may  still  be  active  on 
adequate  stimulation.  This  brief  reference  to  the 
possible  relation  of  the  phenomena  of  the  acute  infec- 
tions to  the  laws  of  natural  selection  and  specific 
chemical  noci-association  has  been  made  as  a  sugges- 
tion. Since  the  doctrine  of  evolution  is  all  or  nothing, 
I  have  included  many  phenomena  to  see  how  reason- 
able or  unreasonable  such  an  explanation  might  be. 

Recapitulation. 

The  following  are  the  principal  points  presented  : 
In  operations  under  inhalation  anesthesia  the  nerve  im- 

37 


pulses  from  the  trauma  reach  every  part  of  the  brain, — 
the  cerebrum  that  is  apparently  anesthetized  as  well 
as  the  medulla  that  is  known  to  remain  awake,  the 
proof  being  the  physiologic  exhaustion  of  and  the  path- 
ologic change  in  the  nerve  cells.  Under  ether  anes- 
thesia the  damage  is  at  least  four  times  greater  than 
under  nitrous  oxide.  Inhalation  anesthesia  is,  there- 
fore, but  a  veneer,  a  mask  that  "covers  the  deep 
suffering  of  the  patient."  The  cause  of  the  exhaus- 
tion of  the  brain  is  the  discharge  of  nervous  energy  in 
a  futile  effort  to  energize  the  paralyzed  muscles  in  an 
effort  at  escape  from  the  injury  just  as  if  no  anesthetic 
had  been  given.  The  exhaustion  is,  therefore,  of  the 
same  nature  as  that  from  over-exertion. 

But  if  the  nerve  paths  connecting  the  field  of  opera- 
tion and  the  brain  be  blocked,  then  there  is  no  discharge 
of  nervous  energy  from  the  trauma,  and  consequently 
no  exhaustion  however  severe  or  prolonged  the  opera- 
tion. 

Fear  is  a  factor  in  many  injuries  and  operations. 
The  phenomena  of  fear  probably  are  exhibited  only  by 
animals  whose  natural  defense  is  nerve-muscular. 
The  skunk,  the  porcupine,  the  turtle,  have  little  or  no 
fear.  Fear  is  born  of  the  innumerable  injuries  in  the 
course  of  evolution.  Fear,  like  trauma,  may  cause 
physiologic  exhaustion  of  and  morphologic  changes  in 
the  brain  cells.  The  representation  of  injury,  which 
is  fear,  being  elicited  by  phylogenetic  association,  may 
be  prevented  by  the  exclusion  of  the  noci-association 
or  by  the  administration  of  drugs  like  morphine  and 
scopolamine,  which  so  impair  the  associational  function 
of  the  brain  cells  that  immunity  to  fear  is  established. 
Animals  whose  natural  defense  is  muscular  exertion, 
among  which  is  man,  mav  have  their  dischargeable 

38 


nervous  energy  used  up  by  fear  alone,  by  trauma  alone, 
but  most  effectively  by  the  combination  of  both. 
What  is  the  mechanism  of  this  discharge  of  energy  ? 
It  is  the  adequate  stimulus  of  the  noci-ceptors  —  the 
electric  buttons  —  and  the  physiologic  response  for  the 
purpose  of  self-preservation.  According  to  Sherring- 
ton, the  nervous  system  responds  in  action  as  a  whole 
and  to  but  one  stimulus  at  a  time.  The  integration 
of  the  individual  as  a  whole  occurs  not  alone  in  injury 
and  fear,  but  also,  though  not  so  strong,  under  other 
phylogenetic  associations,  such  as  the  chase  and  pro- 
creation. When  adequate  stimuli  are  repeated  in  such 
a  rhythm  that  the  new  stimulus  is  received  before  the 
effect  of  the  previous  one  has  worn  off,  a  higher  maxi- 
mum is  reached  than  is  possible  under  a  single  stimu- 
lus, however  powerful. 

Sexual  receptors  are  implanted  into  the  body  by 
natural  selection,  and  the  adequate  stimuli  excite  the 
nerve  muscular  reactions  of  conjugation  in  a  manner 
analogous  to  the  action  of  the  adequate  stimulus  of 
the  noci-ceptors.  The  specific  response  of  either  the 
sexual  receptors  or  the  noci-ceptors  is  at  the  expense 
of  the  total  amount  of  nervous  energy  available  at  the 
moment.  Likewise,  daily  labor,  which,  in  the  lan- 
guage of  evolution,  is  the  chase,  expends  nervous 
energy.  However,  under  the  dominance  of  fear  or 
injury  the  integration  is  most  nearly  absolute  and  prob- 
ably every  expenditure  of  nervous  energy  not  required 
for  efforts  at  self-preservation  is  arrested  ;  hence  fear 
and  injury  drain  the  cup  to  the  dregs.  This  is  the 
potential  difference  between  fear  and  desire,  between 
injury  and  conjugation. 

What  is  the  practical  application  of  this  ?  In  opera- 
tive surgery  there  is  introduced  a  new  principle,  which 

39 


removes  from  surgery  much  of  the  immediate  risk 
from  its  trauma  by  establishing  anoci-association ;  it 
places  on  a  physical  basis  certain  of  the  phenomena  of 
fear  ;  it  explains  to  us  the  physical  basis  for  the  im- 
pairment of  the  entire  individual  under  worry  or  mis- 
fortune ;  the  daily  noci-associations  of  the  individual 
as  a  social  unit ;  or  a  noci-influence  of  a  part  of  the 
body  ;  on  the  other  hand,  it  explains  the  power  of 
therapeutic  suggestion  and  other  influences  which  serve 
for  the  time  to  change  the  noci- integration,  the  physi- 
cal basis  for  the  difference  between  hope  and  despair  ; 
it  explains  some  of  the  phenomena  of  Graves'  disease, 
of  sexual  neurasthenia  ;  possibly  of  hay  fever  and  the 
genesis  of  the  common  cold,  the  principle  is  probably 
equally  applicable  to  the  acute  infections  whose  chem- 
ical noci-association  gives  rise  to  many  of  the  phenomena 
of  the  disease  and  explains  their  cure  by  natural  im- 
munity and  by  vaccines  ;  it  should  teach  us  to  view 
our  patients  as  a  whole  ;  and  especially  should  it  teach 
the  surgeon  gentleness.  It  should  teach  us  that  there 
is  something  more  in  surgery  than  mechanics  ;  and 
something  more  in  medicine  than  physical  diagnosis 
and  drugs. 

Conclusion. 

The  brain  cells  have  existed  during  eons  of  time 
and  amid  the  vicissitudes  of  change  with  perhaps  less 
alteration  than  the  crust  of  the  earth.  Whether 
lodged  in  man  or  in  the  lower  animals,  they  are  related 
to  and  obey  the  same  general  biological  laws,  thus 
binding  them,  that  is,  ourselves,  to  the  entire  past  and 
perform  their  function  on  the  law  of  phylogenetic 
association. 

So  long  have  we  directed  our  attention  upon  tumors, 

40 


infections  and  injuries  that  we  have  not  sufficiently 
considered  the  vital  force  itself.  We  have  viewed 
each  anatomical  and  pathologic  part  as  an  entity,  and 
man  as  an  isolated  phenomenon  in  nature.  May 
we  not  find  in  the  law  of  adaptation  under  natural  se- 
lection, and  the  law  of  phylogenetic  association,  the 
master  key  that  will  open  to  us  the  explanation  of 
many  of  the  pathologic  phenomena  as  they  have  al- 
ready explained  many  normal  phenomena  ? 

And  may  medicine  not  correlate  the  pathologic  phe- 
nomena of  the  sick  man  with  the  forces  of  evolution, 
as  the  naturalists  have  correlated  the  phenomena  of 
the  sound  man, — and  disease  as  well  as  health  be 
given  its  evolutionary  setting  ? 


41 


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COLUMBIA  UNIVERSITY  LIBRARIES  (hsl.stx) 

RD81  C86C.1 

Phylogenetic  association  in  relation  to 


2002293366 


(* 


